The use of high intensity shock waves to comminute renal and urinary calculi has nearly become a standard procedure in Western Europe and the United States. Extracorporeal shock wave lithotripsy (ESWL) is also being used to destroy gallstones at various hospitals in Europe and at several research centers in the US; applications to the FDA for general use in the US have been made. Although these systems are in wide spread use, the basic physical mechanisms whereby the stones are comminuted into small pieces are not clearly understood. Recent evidence indicates that acoustic cavitation (a process whereby microscopic voids within the liquid are made to grow and then collapse violently) is probably a necessary condition for stone comminution. In our preliminary studies of ESWL-induced cavitation, we have determined that this cavitation is sufficiently violent to erode heavy metal plates; calculated temperatures and pressures within tahe collapsing cavities give values as high as one hundred thousand degrees and 5 megabars, respectively. We have demonstrated that this violent cavitation can give rise to copious amounts of free radicals that have a high potential for permanent tissue damage. Recent studies of the optical emissions from cavitation show significant energy in the UV with even more energetic photons likely. We propose a comprehensive and thorough investigation of the role of acoustic cavitation in ESWL. There are two major aspects of this proposal: (i) Cavitation and Stone Comminution--we plan to design and undertake a series of experiments that will elucidate the role of acoustic cavitation in stone comminution, considering in detail the importance of cavitation nuclei, microjet impacts, cavitation-produced shock waves and the characteristics of the host fluid surrounding the stone. (ii) Cavitation Inception and Bubble Dynamics--we plan to undertake a broad study of the fundamentals of acoustic cavitation inception and nonlinear bubble dynamics associated with high intensity shock wave pulses, both from an experimental and a theoretical viewpoint, in order to ascertain the basic physical mechanisms that result in stone comminution and tissue damage,k and to determine the extent to which ESWL-generated acoustic cavitation is machine specific in terms of the violence of individual cavitation events and the number of cavitation events per shock. The goal of this proposed research is to accumulate a wealth of basic information on the role of cavitation in ESWL and, subsequently, to specify application protocols that would ensure that the conditions for stone comminution are optimized and the potential for permanent tissue damage minimized.